Manoalide is a compound isolated from a marine sponge [E. D. de Silva et al., Tetrahedron Letters 21:1611-1614 (1980)] which has anti-inflammatory, immunosuppressive and analgesic properties. Manoalide the structure of which is shown below, includes a 5-hydroxy-2(5H)-furanone moiety, attached in the 4-position of the furanone ring to the rest of the molecule. Certain analogs of manolide, such as seco-manoalide and dehydroseco-manoalide also have anti-inflammatory activity. For further description of the biological activity of manoalide and some of its derivatives reference is made to U.S. Pat. Nos. 4,447,445, 4,786,651, 4,789,749 and to European Patent Application No. 0 133 376 (published on Feb. 20, 1985). ##STR1##
Synthetic analogs of manoalide, particularly analogs having various substituents on the furanone moiety of manoalide, are described in patents and several applications for United States Letters Patent by the same inventor or co-inventor as in the present application, such as U.S. Pat. Nos. 4,935,530 (issued Jun. 19, 1990), 4,957,917 (issued Sep. 18, 1990), 5,013,850 (issued May 7, 1991), 5,037,811 (issued Aug. 6, 1991) and U.S. application Ser. Nos. 699,819 (filed May 13, 1991, pending), 426,243 (filed Oct. 25, 1991, pending), 427,268 (filed Oct. 25, 1989, allowed), 510,364 (filed Apr. 17, 1990, pending), 493,895 (filed Mar. 15, 1990, allowed), 510,367, (filed Apr. 17, 1990, allowed), 693,204 (filed Apr. 30, 1991, pending) and 693,201 (filed Apr. 30, 1991, pending).
Published European Patent Application No. 0 295 056 discloses 4-substituted 5-hydroxy-2(5H)-furanones having anti-inflammatory, immunosuppressive and anti-proliferative activity where the substituents in the 4 position are a variety 1-hydroxy-alkyl, 1-acyloxy-alkyl and 1-carbamoyloxy-alkyl groups.
U.S. Pat. No. 4,855,320 discloses 5-arylalkyl-4-alkoxy-2(5H)-furanones as anti-convulsive and anti-epileptic agents.
Published European Patent Application No. 0 209 274 discloses 4-alkyl-5-hydroxy-2(5H)-furanones as anti-inflammatory and anti-allergy agents.
Chemical Abstracts Volume 107 236559t (1987) discloses 4-acyloxy 5-hydroxy-2(5H)-furanones.
U.S. Pat. No. 4,874,782 describes certain 4-substituted-5-hydroxy 2-(5H)-furanones as agents for treating inflammation, asthma or allergies.
U.S. Pat. No. 4,916,241 describes certain 4-substituted 5-hydroxy-2-(5H)-furanones as agents for modifying the balance between bone production and bone resorption in host animals.
An article by Tanaka et al. "DIANIONS OF --HYDROXY SULFONES: NEW AND GENERAL APPROACH TO SELECTIVE SYNTHESIS OF 2(5H)-FURANONES" Chemistry Letters pp 633-636, 1983 (The Chemical Society of Japan, discloses a synthetic route to 4-alkyl-2(5H)-furanones, including 4-octyl-2(5H)-furanone, and 4-decyl-2(5H)-furanone, without discussing any type of biological activity of these compounds.
An article by Tanis et al. "FURANS IN SYNTHESIS 4. SILYL FURANS AS BUTENOLIDE EQUIVALENTS" Tetrahedron Letters Volume 25, pp 4451-4454, 1984, also describes a synthetic route to 4-alkyl-2(5H)-furanones, including 4-decyl-2(5H)-furanone, without discussing any type of biological activity of these compounds.